A few weeks ago, we wrote about the glimmering ray of hope that had emanated from bad news about potential new Alzheimer's treatments.

Both Bapineuzumab and Solanezumab, the two most progressed new drugs in the development pipeline, had both failed the final stage of their respective clinical trials, and would not be approved by the FDA. However, there was some evidence, and much speculation, that both drugs had shown signs of efficacy in secondary data analyses.

Now, as presented at the American Neurological Association's 2012 annual meeting earlier this week, those secondary analyses have been verified and a newfound optimism has swept the field.

Of course, drug approvals require a massive investment of time and money, and drug companies must always weigh the costs of completing that high risk process, against the benefits they might capture during the few remaining years of the drug's patent life, once the process is completed and the drug is commercialized.

Readers might be surprised to learn that drug companies sometimes abandon effective drugs, if the approval process takes too long and the viable (patent protected) period for recouping their investment is too short. This is the decision that Eli Lilly (Solanezumab) and Pfizer (Bapineuzumab) must now face as they consider the time and cost of next steps to bring these drugs to market.

At this point, there are two encouraging signs that each company might push forward and lobby the FDA for an efficient path to near-term approval. One is that the Federal government, under the National Alzheimer's Prevention Act, is committed to identifying new treatments for this disease. The other, is that the Wall Street analysts, ever pessimistic about success of new AD drugs, have pushed Lilly's stock price upwards in the wake of this new information.

An aging population is the macro-driver of the trend toward increased demand for caregiving. Within that trend, it is cognitie impairment, or declining brain health that is really fueling the growth. A such, caregiving is a topic we watch closely in this blog.

As the geographically dispersed, sandwich generation is increasingly called upon to provide care for an aging parent or relative, long-distance caregiving is also gaining prevalence. Performing this role from afar comes with its own set of challenges, and I am pleased to direct today's readers to the an article posted by Medical E-Compare, a marketer of medical insurance products.

The article offer tips for caregiving from a distance and features a set of practical suggestions for those finding themselves in this role, along with links to additional reources.

Yesterday we commented on the common misdiagnosis of Lewy Body Disease, a problem often mistaken for Alzheimer's Disease. In keeping with that theme, we look today at results from an international physician survey on Alzheimer's diagnoses.

Based on a survey of nearly a thousand physicians in five countries (USA, Japan, UK, France, and Italy), we are not doing a very good job at diagnosing Alzheimer's disease in clinical practice. In fact, about half of all physicians agreed that the disease is "often misdiagnosed" and that diagnoses are "always or often" made too late to treat in a meaningful way.

None of this is news to regular readers of this blog as late detection of cognitive impairment is one of our frequent themes. However, the survey revealed an interesting perspective from the physicians, in terms of "why" they feel diagnoses are so commonly late.

According to the physicians surveyed, the major contributing factors to late diagnosis are:

lack of a definitive diagnostic test;

lack of communication from patients/caregivers; and

stigma

Not mentioned among their reasons is the one glaring problem that primary care physicians confess to me on a regular basis. I hear frequently from physicians that investigating memory complaints takes too much time, and often leads to a diagnosis of a problem they don't feel they can treat effectively. This perspective often leads them to "just keep an eye on the concern" until symptoms worsen and the need for medical intervention is clear. As the survey noted, this is "too late".

Managing the cognitive health of an aging population is a complex problem, and a difficult one to approach within the confines of our current "fee for service" healthcare system. As new models evolve, like the Accountable Care Organizations described in the Healthcare Reform Act, we will have an opportunity to greatly improve our standards of care in this important field.

While this blog strives to clarify the daily news about brain health, sometimes it serves best by simply "emphasizing" the news about brain health. A very well reported article about Lewy Body Dementia, published in the The New Old Age blog of the NYTimes, is worthy of such emphasis today.

Like Alzheimer's disease, Lewy Body disease is a debilitating brain disorder that impairs cognition and leads to dementia. However, because the symptoms are similar, it is often mis-diagnosed as Alzheimer's disease, and subsequently mis-treated.

A key difference between the two diseases is in their most typical initial symptoms: short term memory disruptions are most typical in Alzheimer's disease, whereas executive function (completing complex tasks) and visual/spatial abilities are most commonly the first impairments noted in Lewy Body disease.

Along with low awareness of Lewy Body disease, symptomatic similarities to Alzheimer's disease are two drivers of mis-diagnosis. Making matters worse, other common symptoms, such as rigidity and altered gait, sometimes lead to mis-diagnoses as Parkinson's disease.

Hopefully, with growing awareness and the formation of organizations like the Lewy Body Dementia Association, clinical efforts to correctly diagnose and treat this disease will continue to gain efficacy.

What's with every disease and medical condition having a day or month geared toward raising awareness? Are such efforts effective? Wouldn't it be better to put our time and energy into new treatments and cures?

Those are fair questions.

Here's a link to a great argument in support of Alzheimer's awareness, and why awareness matters. The article explains how heightened awareness can drive real benefits in five important ways, each of which are carefully explained in the full article:

It is easy to overlook “awareness” as an important part of the solution to the Alzheimer’s problem. This is especially true given the clear need for better treatment. However, a little reflection on the benefits of awareness, weighed against the relative ease with which we can spread information today, shows the massive benefits of greater awareness.

Awareness matters. Please do your part to increase awareness by clicking through, and then reading and sharing the article with your online social networks.

The stated purpose of this blog is to clarify the daily news about brain health. Certainly, a lot of the reporting in this space needs to be filtered and contextualized for clarity. But not all of it.

I noticed a very well-written article published today in the Pacific Standard, describing research about the relationships between high calorie diets and memory loss, as well as between obesity and overall cognition. I will summarize the main points below but I encourage you to click through and read this excellent piece of reporting.

According to a Mayo Clinic study published in the Journal of Alzheimer's Disease, high calorie diets (exceeding a threshold of 2143 calories/day) are associated with higher risk for cognitive impairment among the elderly. The article also summarizes other research concluding that obesity in mid-life is a risk factor for dementia, and that weight loss can improve memory and organizational skills.

Overall, this is a well-organized summary of evidence that managing cardiovascular health through proper diet may have a clear and significant impact on overall cognitive health.

As our population simultaneously ages and becomes more obese, poor cardiovascular health has driven the incidence of certain medical conditions ever higher. For example, general awareness and acceptance of transient ischemic attacks, alternatively known as TIA's and mini-strokes, has risen notably over the past two decades.

While awareness of medical conditions and the risks that cause them is generally a good thing, a false comfort, based on a perception of "good medical outcomes", can be quite dangerous.

Sticking with the example of TIA's, the tone of much public discourse on such a clear symptom of severe cardiovascular disease, has been somewhat benign. Because "mini-strokes" are common, and immediate outcomes are often fairly good, we may be developing a false notion that a mini-stroke is a minor occurrence. On the contrary, a mini-stroke is a serious sign that immediate, medical attention is needed.

A recent study published in the journal Stroke showed that lingering disabilities, following a mini-stroke, are highly prevalent. In fact, about 15% of patients who had a single TIA had lingering disabilities after three months and, for those who had a series of TIA's, more than half (53%) had lingering disabilities.

More importantly, TIA's are a major warning sign of an underlying problem that could lead to a much bigger stroke and major debilitation of the brain. While the symptoms of a small stroke may fade quickly, immediate medical attention is still required. Ignoring such events could lead to dire consequences including death.

The term "Mini-Stroke" may connote an insignificant event, but the evidence suggests that any stroke is serious, and the concept of "mini" might be misleading in terms of its health-related consequences.

On the one hand, we all know intuitively that our diet effects the way we feel. Many of us feel tired after a heavy meal, many of us are irritable when hungry, and many of us are familiar with the boost/crash cycle of eating sugary snacks. Most would also agree that a light, nutritious meal makes us feel differently than one based on junk food.

On the other hand, many claims about certain foods and their impact on brain health, have been either overblown or misinterpreted by the masses. As far as we know, there is no particular oil, berry, fish, root, herb, or vegetable that we should all start consuming in massive quantities, as a means to an immediate improvement in brain function.

Rather, it is important to think about diet and the brain in both the short term and the long term. This is true because dietary habits have both short-term and long-term effects on the brain.
Guidelines for a healthy brain diet have been discussed here and elsewhere many times.

The point of today's post is to emphasize the importance of the word "habit" in the phrase "dietary habit".
If you consistently consume a lot of preservative filled, sugar laden, trans fat based snacks, you can't undo the damage with a giant bowl of spinach and a glass of fish oil. Despite claims you may read about coconut oil, green tea, and gingko biloba, don't fool yourself into thinking that you can add those elements to a poor diet and your brain will be fine.

If you only read the headlines, and not the news beneath those headlines, you might be inclined to think that a certain class of blood pressure medications (angiotensin receptor blockers) can prevent Alzheimer's disease.

A recent publication in Archives of Neurology has spawned a number of sensational headlines about Alzheimer's prevention. The study showed that, among nearly 900 subjects who died at old age and had brain autopsies, those who had taken angiotensin receptor blockers had fewer amyloid plaques in their brains. This was true of patients with Alzheimer's disease, patients with other causes of dementia, and patients with normal cognitive health.

Amyloid plaques in the brain are a hallmark sign of Alzheimer's disease, but it is not yet well understood if the plaques are the cause of the disease, or if they are a protective response by the brain against some other biological process. For this reason, it would be a great leap to suggest that blood pressure drugs could play a role in treating Alzheimer's disease. While that might be true, it is equally possible that such drugs could play a role in preventing the body's natural attempt to protect itself from other facets of the disease process.

Every new clue is useful in assembling the big picture and understanding this complex disease. This study yielded a great finding, an interesting correlation, and the possibility of new insights. But as far as we know, it did not uncover a preventative treatment for Alzheimer's disease.

We've all been hopeful that a new class of Alzheimer's drugs (monoclonal antibodies) would soon bring effective treatment to the growing number of Alzheimer's patients.

The latest approach is based on using antibodies that bind with harmful amyloid protein. The idea is that the antibodies will be naturally flushed from the body by the immune system, and take the harmful amyloid away as well.

Major trials have now concluded on two such drugs: Bapineuzumab and Solanezumab. The primary outcome measures of these trials were "improved cognition" and/or "improved function" versus a placebo group. That is to say, if subjects who took these drugs had either better cognition or better physical ability to perform daily activities, compared to subjects who did not, then the drugs were probably effective enough to be approved by the FDA. On these measures, all trials have failed.

But that is not necessarily the end of the story for either drug.

A secondary analysis, performed on a combination of the data from the multiple Solanezumab trials, shows a small improvement in cognition among treated subjects. It is a weak signal, but it provides some hope on which to build. Especially noteworthy is that the positive effect was most evident in the earlier stage patients with healthier brains.

A stronger signal has come from a look at the targeted biomarkers (amyloid and tau proteins) that these drugs target.

Researchers have speculated (and common sense has suggested), that using such drugs to remove amyloid from the brains of subjects who have already suffered a fair amount of brain damage, may not be helpful. The obvious experiment would be to remove the amyloid at an earlier stage, before brain damage occurs, which is before symptoms of memory loss and other cognitive decline are noted. This makes intuitive sense and is well-aligned with the possible effect detected in the Solanezumab trial on early stage subjects.

As such, a key indictor of the true potential for each drug may be actual measures of amyloid reduction in those subjects who were treated. Researchers involved in the Bapineuzumab trial announced yesterday that the drug did in fact dramatically reduce amyloid in the brain and spinal fluid of trial subjects. Similar biomarker data from the Solanezumab trial is expected in the coming weeks.

Overall, we wish that the drugs had produced great improvements in cognition and function. While those goals were not met, it is encouraging to note that some, small measure of cognitive improvement may have been realized in the Solanezumab trials, and a clear reduction in amyloid protein was seen in the Bapineuzumab trials.

This leaves us with a hopeful hypothesis that, if used on subjects at an earlier stage of Alzheimer's disease, before extensive brain damage has occurred, either or both drugs may yield more effective treatment than what is currently available.

Mild Cognitive Impairment (MCI) is a term we are seeing more and more frequently in the general press. Unfortunately, efforts to clarify its meaning often serve to further confuse the issue.

Case in point is a lengthy discussion about MCI, with an associate professor of psychiatry, published recently in the New York Times "New Old Age" blog. While lots of important ground is covered in the interview, most of the information is geared toward MCI caused by Alzheimer's disease, without proper emphasis and clarity about other, arguably more common causes of MCI. Population-based studies suggest that prevalence of MCI cases caused by depression, poorly controlled diabetes, sleep-disorders, thyroid conditions, alcohol/drug abuse, medications, and cancer treatments, far exceed the number of cases caused by early stage Alzheimer's disease.

That oversight, that most MCI is caused by common, treatable, medical conditions and not early Alzheimer's disease, undermines the clarity of the piece. Most of the discussion is geared toward understanding MCI caused by Alzheimer's disease, as opposed to MCI caused by the many other, more common, medical conditions that impair cognition.

This confusion about MCI and the proclivity to attribute MCI to Alzheimer's disease are not new phenomena. I wrote about it more than three years ago in a post about MCI converting to Alzheimer's disease. In the years since, increased interest in cognitive health has brought increased coverage of these issues. Unfortunately, much of the coverage is poorly presented and does not aid clarity.

Here is a constructive way to understand the term MCI: While some decline in cognitive function is normal with aging, MCI refers to changes that are more severe than would be expected at a given age, but not so severe as to prevent a self-reliant lifestyle. When cognitive decline is severe enough to prevent self-reliance, we use the term "dementia". In this way, cognitive health can be viewed as a continuum from "normal aging" to "MCI" to "dementia". One crosses from MCI into dementia when the cognitive decline is severe enough to prevent effective self-care.

Recent history has not been kind to R&D efforts aimed at developing new Alzheimer's drugs. While four approved drugs can help manage symptoms of the disease, and perhaps slow its progression to a small degree, the field has aggressively pursued new treatments that can significantly slow or stop progression.

These efforts have been hampered by the complexity of the disease and by, what most experts consider, a fairly rudimentary understanding of its pathology. We understand that Alzheimer's disease manifests as a decline in cognitive function, and that the decline is caused by a loss of brain cells and the connections between them. We also understand that an accumulation of amyloid proteins in the brain, and a chemical change in Tau proteins (phosphorylation) in the brain, are major factor contributing to that loss of brain cells.

However, the picture becomes less clear when we try to identify the many possible processes that start the pathology. The answer may be related to cell metabolism, to brain chemistry, to inflammation, or trauma, just to name a few of the leading areas of scientific inquiry. Probably, a host of these processes interact and lead to a cascade of biological responses along the way.

The questions to which we do not yet have solid answers are: which processes matter most, are they inter-related, and why do they lead to this disruptive outcome? Without those answers, it is difficult to develop drugs that will target the right process, at an early stage. It is a very complex problem involving the most complex of organs.

Nonetheless, research persists and scientific efforts are ongoing. At this point, several promising agents are moving along the pathway in FDA clinical trials. A good overview of the Alzheimer's pipeline was recently published by Fierce Biotech. It is slightly technical, and geared toward financial analysts, but it is comprehensive and gives a good foundation of the theory behind each approach.

The link goes to a WebMD presentation of 21 slides that can be viewed and read in about 5 minutes. For anyone over age 40, or with an interest in depression, I highly recommend clicking through and reading; it is very well done and informative.

According to a recent study published in Neurology, there may well be a relationship between memory and nicotine. But before you run out and take up smoking, let's examine the facts.

First, the study was conducted on a small number of participants (74), all of whom had a mild, prior memory deficit, and the nicotine was delivered through a transdermal patch, not through smoking cigarettes. After six months, those who had received a nicotine patch outperformed a placebo group on cognitive tests of attention and memory. In fact, the group receiving nicotine improved their baseline scores while the placebo group showed a decline in thinking abilities over the six month trial.

For sure, the well-documented risks associated with smoking (which include cognitive decline) would preclude any reasonable argument about smoking to preserve brian health. But nicotine, if delivered without the burden of smoking, has been shown to interact with receptors in the brain and improve some chemical signals along neural circuits. It is more than plausible that this is a benefit we could one day harness for improved cognition.

The major caveats on this particular study are that it was very small, the noted cognitive gains were considered minimal, and many of the authors work for companies that sell nicotine patches. Nonetheless, this early stage work is noteworthy and bodes well for future benefits.

The National Alzheimer's Prevention Act, signed into law one year ago, calls for a national strategy for defeating this terrible disease. A late-stage draft of the strategy sets a goal to develop a cure by the year 2025. While many have suggested a timeline with more urgency, say by 2020, others have suggested that this timeline is too ambitious.

On the one hand, given our still poor understanding of the disease, coupled with a dismal track record of success for pipeline drugs over the past decade, it seems unlikely that a cure could be developed prior to 2025. In fact, against the backrop of recent evidence, it may well take longer than that.

On the other hand, we could stop short of a cure and still have great success. For example, many chronic diseases like diabetes and hypertension have no cure, but we have effective treatments, and we manage those diseases with high efficacy. It is likely that new drugs, developed well before 2025, will give us greater treatment benefits for patients with Alzheimer's.

Perhaps of greater importance is the fact that we already have approved therapies that can significantly slow Alzheimer's disease progression. However, since we commonly detect the disease too late and intervene only after massive brain damage has occurred, the perception among physicians is that treatment is unhelpful. This nihilistic perception actually perpetuates the cycle of late intervention because, believing that there is no treatment, many MDs don't look for early signs Alzheimer's.

In this regard, a key element to an effective national Alzheimer's strategy would be to update physicians about the benefits of early detection and equip them with the tools and training to proactively monitor the cognitive health of their patients. When a cure is developed, that will be great. But in the meantime, we can find the disease early and treat it as effectively as possible with robust therapy (drugs, diet, physical exercise, control of diabetes and hypertension, intellectual stimulation, social engagement, and caregiver education). Such a comprehensive approach has been shown to significantly delay disease progression in a meaningful percentage of early-stage patients.

MCI is a subtle loss of thinking ability, such as impaired memory or judgment, that is not severe enough to interfere with the person's normal activities of living. The study showed about a 20% incidence rate which is squarely in line with previous estimates.

The press has been largely focused on the fact that, in this study, men between the ages of 70 and 89 years had a higher incidence of MCI than women of the same age. This is probably true. It is also probably easy to explain.

MCI is not a disease, it is merely a descriptor term for a certain level of cognitive impairment. It refers to the degree of impairment that falls between normal cognition and the severe loss of function that we call dementia. Asking "why" a person has MCI is a whole different question with a host of common answers including depression, thyroid disease, stroke, sleep disorder, Alzheimer's disease, and anxiety, to name just a few.

The question of "why" a person has MCI was not adressed in this study, but may shed some important light on the observed gender differences. For example, sleep disorders and certain cardiovascular conditions, like hypertension and stroke, are common causes of MCI and are somewhat more prevalent among men than women. Clearly, conditions that impair memory and are also more common in men, could fully explain the observed gender differences in this study. In that respect, these results are hardly surprising and, in fact, make perfect sense.

It would be truly worthy of a media frenzy if researchers controlled for each cause of MCI and still found that one gender was more susceptible than the other. But despite many misleading headlines, that was not the case in this study.

As genetic testing has become more commonplace in medicine, we have all seen frequent examples of overstatement, where writers and speakers confuse "higher risk" with "absolute certainty". This has been an especially maddening component of arguments against testing for the APOe4 gene associated with increased risk for Alzheimer's disease.

A great many of these faulty arguments state that learning about a genetic risk for an incurable disease is pointless. (I have refuted that argument many times but that is not the point of this post). This week, research published in Archives of Neurology strengthens the case for genetic testing.

In a study from the University of Washington in St. Louis, more than 200 participants aged 45 to 88 reported on their physical exercise habits and submitted to spinal fluid measures or PET scans to determine the amount of accumulated amyloid protein in their brains. They also had their APOe4 status checked and researchers found that, among those who carried the APOe4 gene, regular exercisers had less amyloid load than sedentary members of the group. Interestingly, this was not the case among the APOe4 non-carriers.

This was a small study and needs replication before we can conclude that physical exercise staves off amyloid accumulation in those with genetic risks for AD. However, the study has a very intuitive finding and gives credence to a much larger body of work showing that good cardiovascular health may reduce the risk of Alzheimer's disease.

The suggestion from this study is very significant. It could be that genetic risk for AD (usually considered to be an unmodifiable risk), could possibly be reduced by physical exercise. If so, it will put a whole new spin on those old arguments against genetic testing.

As we noted here late last year, there are several promising new Alzheimer's treatments in the FDA pipeline. While the early stages of the pipeline are predictably more full than the later stages, we expect to see data this year on at least two agents that are nearing the end of the trial process.

Earlier this week, Baxter announced the successful conclusion of their futility analysis on IVIG for treating symptoms in mild to moderate stage Alzheimer's patients. The futility analysis, conducted by the Data Safety and Monitoring Board (DSMB), indicated that further trial efforts could proceed with no modification to the protocol. With that result, Baxter immediately announced plans to initiate a confirmatory Phase III trial to begin in early 2012.

IVIG, or intravenous immunoglobulin, has been marketed for some 25 years to treat autoimmune diseases, but has not previously been studied and approved for treating Alzheimer's disease. Given it's historical safety profile and early data indicating efficacy in Alzheimer's patients, it may be the next drug approved in this field.

Cognition, or thinking ability, is a complex concept and is difficult to measure. Nonetheless, many studies have shown that intellectual activity seems to be correlated with some measure of"better cognition". This makes intuitive sense and has given rise to many "use it or lose it" type slogans aimed at our aging population.

In a study published online today in the Archives of Neurology, researchers from Berkeley's Neuroscience Institute found that, seniors who pursued intellectual hobbies throughout their lives, accumulated less amyloid plaque in their brains later in life. This is interesting in a couple of ways.

First, while cognition can be difficult to measure, accumulated amyloid plaque in the brain has become increasingly easier to measure with new agents that bind to amyloid and "light up" during a PET scan of the brain. We can now get a fairly accurate read of amyloid load which is, by all accounts, much more tangible than our best measures of cognition.

An important caveat to this point is that, while we can accurately measure the amount of amyloid in the brain, we are still somewhat unclear on what that means. For sure, amyloid accumulation is neurotoxic (harmful to brain cells), but such accumulation may be a reaction to some other disease process that would be even more damaging without the presence of amyloid plaques. This is a topic of intense, ongoing study.

The second interesting take-away from this new research is that the subjets reported a lifetime of intellectual activity. If this work is repeated in larger studies and deemed to be conclusive, it will not mean that playing bridge and studying music in retirement will keep amyloid plaques out of the brain. It may be that an entire lifetime of brain exercise is the minimum threshold for a meaningful benefit.

In any case, it is very encouraging to see pathological evidence supporting the theory that brain exercise can have cognitive benefits during our elder years. We will watch ongoing research in this area with great interest.

I am encouraged by the top-level recognition of Alzheimer's as a major social problem, and by the seeming seriousness of the current administration to tackle it. However, the lack of funding in these fiscally challenging times is concerning. For perspective, we commit more than $6B annually in federal funds to cancer research compared to about a half a billion for AD research. Current lobbying efforts are aiming for a $2B budget to implement a strategy under NAPA.

If we are to wage a war against this disease, then research funds to better understand Alzheimer's and to develop a cure must be the center-piece of the strategy. However, I hope that the planners do not overlook more certain, and more immediate opportunities to win many battles. Great progress can be achieved with not much more than a dose of pragmatism and public will. I described those opportunities in some detail in an earlier post "Antidote for the Alzheimer's Epidemic".

Given the fast pace of research in this field over the past decade, coupled with historically slow adoption of new knowledge into clinical practice, there is a large gap between the state of our medical knowledge and the standards of care we commonly practice in the clinic.

So let's commit to a national plan for thwarting Alzheimer's and focus on developing a cure. But let's make sure we also take care to update clinical practice with all of the new discoveries we have made, and will continue to make, as we race toward that ultimate goal.

Dimebon, an experimental Alzheimer's treatment, has failed its Phase III clinical trial, and will not be further developed by its co-sponsors, Pfizer and Medivation.

The Associated Press article reporting on this failure described it as a "major setback" but it really comes as no surprise to those who have followed the trajectory of this potential new drug.

As we described in an earlier post, Dimebon failed its initial trial showing no cognitive benefits and no improvement of function among those research subjects who took it. Undaunted by the initial failure, the drug's sponsors pushed forward with three additional trials: one measuring the drug's effect over a longer period, one measuring the drug's effect as poly-therapy in conjunction with Aricept, and one measuring the drug's effect in patients with Huntington's disease. All three trials have now failed.

This is not good news for the field but I think it important to comment on how this might effect attitudes toward further research. By and large, even the first Dimebon failure in March of 2010 was expected by most experts who follow this space. Despite the fact that Pfizer and Medivation chose to push forward and complete three additional studies, consensus was that the drug was unlikely to be effective, and success in those trials was considered an absolute long-shot.

Now, those expectations have been met, and no one is really surprised. Research will continue at a cautious but steady pace, perpetually fueled by the lucrative potential of success.

According to the Center for Disease Control and Prevention, longevity has ticked up in America with life expectancy climbing to almost 79 years.

Homicide and cancer, two prominent causes of death, both declined in the past year and contributed to longer lives across the American population. This is good news overall, but belies a trend that will continue to redefine which risks and priorities demand our national focus.

An obvious implication of a longer life span is that medical conditions correlated with aging will become more prevalent. This portends a rising incidence of Alzheimer's disease as a higher percentage of the population lives will into the years when they are most at risk for that terrible disease.

We all want to live longer, healthier lives and the general trend suggests that each of us enjoys a rising likelihood that we will do so. But as we all traverse the lengthening arc of our elder years, we must face a shifting set of threats to our livelihood. In today's reality, one of the key risks we must prepare to manage in the final years of our projected lives, is the risk of dementia caused by Alzheimer's disease.

Fortunately, a vast research effort is underway to identify manageable risks for AD and to develop guidelines for minimizing the likelihood of suffering its consequences. We review that research on a regular basis in this blog and strive to keep our audience abreast of the latest developments in this important field.

It's been a long time coming, but the FDA might finally have enough evidence to allow bio-marker measures into clinical trials for Alzheimer's treatments. This change could potentially speed the trial process, reduce the risk of failed trials, and yield new AD therapies in the near future.

Based on an analysis of prior publications about bio-markers for Alzheimer's disease, an expert panel convened by the Alliance for Aging Research and the FDA, found ample scientific evidence for including changes in bio-markers as outcome measures in FDA clinical trials. This means that, rather than relying solely on measures of cognition and function (which are measures of worsening symptoms), a drug could now be approved based on its ability to prevent pathological changes that are only evident through an examination of bio-marker measures.

An obvious precedent for this approach comes from the cholesterol field. Since high cholesterol is a condition with no immediately apparent symptoms, a trial based on symptomatic improvement would always fail. To approve cholesterol reducing drugs, the FDA allowed trial designs that used blood-based measures of cholesterol as a bio-marker, in lieu of any symptoms produced by a high cholesterol level.

It has long been known that Alzheimer's disease is characterized by a series of pathological changes. These changes progress from shifting protein levels in the spinal fluid, then to lesions in the brain, and eventually to brain atrophy. However, the precise relationship between the disease and these pathological changes had not been well enough understood for the FDA to allow their measures as part of a clinical trial. With a massive research focus over the past five years and what appears to be an objective, expert review of the evidence, it appears as though future trials may well include bio-marker measures as critical trial outcomes.

Many Alzheimer's related stories get massive press coverage, despite minimal importance in the grand scheme of our efforts to thwart the disease. This story has been relatively uncovered in the mainstream, but might well be one of the most important stories of the year.